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Wang F, Xu Y, Chen Y, Wang X, Xu Q, Xia H, Yuan K, Dong Y, Liu L, Wang W. HCC patients with triple positive tumor markers may benefit from post-surgery adjuvant treatment. J Gastrointest Surg 2025:102075. [PMID: 40315954 DOI: 10.1016/j.gassur.2025.102075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 04/15/2025] [Accepted: 04/25/2025] [Indexed: 05/04/2025]
Abstract
PURPOSE To explore the correlation between the number of positive tumor markers and clinical-pathological-ultrasonic-prognostic characteristics of hepatocellular carcinoma (HCC), and to determine the importance of postoperative adjuvant therapy in HCC patients with different number of positive tumor markers. METHODS This retrospective study analyzed 649 HCC patients. The relationships between clinical-pathological-ultrasonic characteristics and 3 tumor markers, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP) and lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), were analyzed. Cumulative recurrence-free survival (RFS) was analyzed according to the number of positive tumor markers, and according to with or without postoperative adjuvant therapy in each group. RESULTS The expression patterns of 3 tumor markers were related with transaminase, maximum diameter, microvascular invasion (MVI), macrovascular invasion, satellite nodule, echogenicity consistency, morphology, color doppler flow imaging (CDFI) pattern, and wash-out degree. Traditional Chinese Medicine (TCM) was the predominant intervention (32.00%) in triple negative group, and transarterial chemoembolization (TACE) monotherapy was the most common intervention in single positive group (42.99%), double positive group (39.51%), and triple positive group (35.48%). Cox proportional hazards regression analyses revealed that positive tumor markers were associated with poor RFS. There was a significant different between triple positive group patients with post-operative adjuvant therapy and patients without post-operative adjuvant therapy (30.0 months vs. 19.6 months, P=0.019). CONCLUSION The number of positive tumor markers had different clinical-pathological-ultrasonic-prognostic characteristics. Pre-operative serum tumor markers provided a more convenient and noninvasive method to select patients with high risk of recurrence, thus can make more appropriate surgical strategies and postoperative adjuvant therapy.
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Affiliation(s)
- Feihang Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yadan Xu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yanni Chen
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Qingyue Xu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Hansheng Xia
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Kai Yuan
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yi Dong
- Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
| | - Lingxiao Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
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Huang Z, Lin XJ, Li SS, Luo HC, Li KY. Differentiating atypical hepatocellular carcinoma from focal nodular Hyperplasia: The value of Kupffer phase imaging with Sonazoid-Contrast-Enhanced ultrasound compared to Gadodiamide-Enhanced MRI. Eur J Radiol 2025; 184:111991. [PMID: 39954323 DOI: 10.1016/j.ejrad.2025.111991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/06/2025] [Accepted: 02/06/2025] [Indexed: 02/17/2025]
Abstract
OBJECTIVE This study aims to evaluate the value of Kupffer phase imaging with Sonazoid-Contrast-Enhanced Ultrasound (CEUS) in differentiating atypical Hepatocellular Carcinoma (HCC) from Focal Nodular Hyperplasia (FNH), compared to the efficacy of Gadodiamide-Enhanced Magnetic Resonance Imaging (CEMRI). METHODS We retrospectively reviewed a total of 56 focal liver lesions, comprising 36 atypical HCC and 20 FNH lesions, which were examined pre-operatively using both CEUS and CEMRI. Features were extracted from the images obtained from both modalities. The diagnostic performance of these features was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUC). RESULTS In the multivariate analysis, HBsAg-positive status (OR = 8.395, p = 0.021) and hypo-enhancement in the Kupffer phase (OR = 5.276, p = 0.042) were identified as independent predictors of atypical HCC. The specificity and sensitivity of HBsAg-positive for diagnosing atypical HCC are 65.0 % and 91.7 %, respectively. The specificity and sensitivity of hypo-enhancement in the Kupffer phase for diagnosing atypical HCC are 95.0 % and 63.9 %, respectively. Significantly, by integrating CEUS diagnostic characteristics to distinguish atypical HCC from FNH, we attained a specificity of 100.0 %, a sensitivity of 63.9 %, and a diagnostic accuracy of 76.8 %. Similarly, the combination of CEMRI diagnostic features resulted in a specificity of 100.0 %, a sensitivity of 47.2 %, and an overall diagnostic accuracy of 66.1 %. CEUS's diagnostic accuracy is superior to CEMRI and this difference is statistically significant (P < 0.05). CONCLUSION Sonazoid-CEUS demonstrates significant clinical potential and is a viable tool for the differential diagnosis of atypical HCC and FNH.
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Affiliation(s)
- Zhe Huang
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District Wuhan City Hubei Province China.
| | - Xiao-Jing Lin
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District Wuhan City Hubei Province China.
| | - Shan-Shan Li
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District Wuhan City Hubei Province China.
| | - Hong-Chang Luo
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District Wuhan City Hubei Province China.
| | - Kai-Yan Li
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District Wuhan City Hubei Province China.
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Kallenbach M, Qvartskhava N, Weigel C, Dörffel Y, Berger J, Kunze G, Luedde T. [Contrast-enhanced ultrasound (CEUS) for characterisation of focal liver lesions]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:952-970. [PMID: 37798924 PMCID: PMC11211032 DOI: 10.1055/a-2145-7461] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 06/21/2023] [Indexed: 10/07/2023]
Abstract
Due to the trend towards increased use of imaging and rising awareness among high-risk patients, gastroenterologists and hepatologists are more frequently confronted with patients with focal liver lesions. In the differentiation of these lesions, CT and MRI have increasingly found their way into primary diagnostic steps in everyday clinical practice. Contrast-enhanced sonography, on the other hand, is a very effective and cost-efficient method for assessing focal liver lesions. The success of the method is not only based on the visualisation of microvascularisation in real time. If sonography is performed by the treating physician, he can use the exact knowledge of history and clinical findings to specifically adapt the examination procedure and to interpret the sonographic findings with greater accuracy ("clinical sonography"). At the same time, the method enables the practitioner to combine diagnostics and management decisions in his or her own hands. To achieve excellent results with contrast-enhanced sonography-as with any other imaging method-it is necessary that the examiner is sufficiently qualified.This article systematically presents the sonographic characteristics of the most common liver lesions and clearly shows their contrast patterns using videos (available via QR code). The article illustrates that CEUS could-and from the authors' point of view, should-have an even greater significance in the future.
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Affiliation(s)
- Michael Kallenbach
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Natalia Qvartskhava
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christian Weigel
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Yvonne Dörffel
- Medical Outpatient Department, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Jens Berger
- Ernst von Bergmann Klinikum, Department of Gastroenterology, Hepatology, Infectious Diseases and Rheumatology, Potsdam, Germany
| | - Georg Kunze
- Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH, Villingen-Schwenningen, Germany
| | - Tom Luedde
- Department of Gastroenterology Hepatology and Infectious Diseases, University Hospital of Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
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Zhou F, Sun Y, Hou Y, Liu F, Yu X. Intratumoral perfusion may affect microwave ablation area of hepatocellular carcinoma. Int J Hyperthermia 2023; 40:2268892. [PMID: 37927295 DOI: 10.1080/02656736.2023.2268892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 10/05/2023] [Indexed: 11/07/2023] Open
Abstract
OBJECTIVES We aimed to evaluate the effect of intratumoral perfusion on microwave ablation (MWA) area in hepatocellular carcinoma (HCC). METHODS Patients who underwent curative MWA for HCC between October 2013 and May 2015 were enrolled. Three days before MWA, contrast-enhanced ultrasound (CEUS) was performed to illustrate the perfusion characteristics of the target lesion. Using the Sonoliver quantification software, time-intensity curves of dynamic CEUS were obtained, and quantitative parameters were extracted. Two microwave antennae were inserted into the center of the tumor and MWA was performed with a continuous power output of 50 W for 5 min. A second CEUS was performed to measure the size of the ablated region. Thereafter, an additional MWA procedure was performed until complete ablation with a 5-10-mm safety margin was achieved. RESULTS A total of 38 patients who underwent curative MWA for 39 HCC nodules were enrolled. The mean age was 57 years (34-80 years), and the median maximum diameter of the HCC was 3.4 cm (interquartile range, 2-6.8 cm). Time-intensity curves were obtained and the area under the curve (AUC) was selected as a parameter for intratumoral perfusion. The AUC was inversely and linearly correlated with the size of the MWA area, including long- and short-axis diameters and ablation volume. A 1,000-dB·s change in the AUC produced an average change of 1.17 ± 0.44 mm, 0.725 ± 0.355 mm, and 2.4995 ± 0.6575 cm³ in the long- and short-axis diameters and ablation volume, respectively. CONCLUSIONS The intratumoral perfusion of HCC was inversely correlated with MWA area size.
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Affiliation(s)
- Fubo Zhou
- Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing, China
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Ya Sun
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Yaxin Hou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
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Qin X, Hu X, Xiao W, Zhu C, Ma Q, Zhang C. Preoperative Evaluation of Hepatocellular Carcinoma Differentiation Using Contrast-Enhanced Ultrasound-Based Deep-Learning Radiomics Model. J Hepatocell Carcinoma 2023; 10:157-168. [PMID: 36789250 PMCID: PMC9922506 DOI: 10.2147/jhc.s400166] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 01/28/2023] [Indexed: 02/10/2023] Open
Abstract
Objective Distinguishing the degree of differentiation, hepatocellular carcinoma (HCC) has important clinical significance in the therapeutic decision-making and patient prognosis evaluation. Methods We developed a deep-learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) to evaluate the differentiation of HCC noninvasive. We retrospectively analyzed HCC patients who had undergone resection and CEUS one week preoperatively between November 2015 and August 2022. Enrolled patients were randomly divided into training (n=190) and testing (n=82) cohorts in a 7:3 ratio. The depth of learning and radiological characteristics reflecting the differentiation degree of HCC were extracted, and the least absolute shrinkage and selection operator(LASSO) was used for feature selection to obtain the most valuable features and then build a DLR model based on the useful features. Results The deep-learning Radiomics model could accurately predict the degree of differentiation of HCC; the area under the curve of the DLR model in the training and testing cohorts was 0.969 and 0.932, respectively. The accuracy, sensitivity, and specificity of the CEUS-based DLR model for predicting the differentiation of HCC were 0.915, 0.938, and 0.900, respectively, in the testing cohort. The decision curve analysis confirmed that the combined model predicted good overall net income for differentiation. Conclusion The CEUS-based DLR model provides an easy-to-use, visual, and personalized tool for predicting the differentiation of HCC and can help doctors formulate more favorable treatment plans for patients.
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Affiliation(s)
- Xiachuan Qin
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China,Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China
| | - Xiaomin Hu
- Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China
| | - Weihan Xiao
- Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China
| | - Chao Zhu
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Qianqin Ma
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China
| | - Chaoxue Zhang
- Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China,Correspondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86-13955158023, Email
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Sabeti S, Ternifi R, Larson NB, Olson MC, Atwell TD, Fatemi M, Alizad A. Morphometric analysis of tumor microvessels for detection of hepatocellular carcinoma using contrast-free ultrasound imaging: A feasibility study. Front Oncol 2023; 13:1121664. [PMID: 37124492 PMCID: PMC10134399 DOI: 10.3389/fonc.2023.1121664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/21/2023] [Indexed: 05/02/2023] Open
Abstract
Introduction A contrast-free ultrasound microvasculature imaging technique was evaluated in this study to determine whether extracting morphological features of the vascular networks in hepatic lesions can be beneficial in differentiating benign and malignant tumors (hepatocellular carcinoma (HCC) in particular). Methods A total of 29 lesions from 22 patients were included in this work. A post-processing algorithm consisting of clutter filtering, denoising, and vessel enhancement steps was implemented on ultrasound data to visualize microvessel structures. These structures were then further characterized and quantified through additional image processing. A total of nine morphological metrics were examined to compare different groups of lesions. A two-sided Wilcoxon rank sum test was used for statistical analysis. Results In the malignant versus benign comparison, six of the metrics manifested statistical significance. Comparing only HCC cases with the benign, only three of the metrics were significantly different. No statistically significant distinction was observed between different malignancies (HCC versus cholangiocarcinoma and metastatic adenocarcinoma) for any of the metrics. Discussion Obtained results suggest that designing predictive models based on such morphological characteristics on a larger sample size may prove helpful in differentiating benign from malignant liver masses.
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Affiliation(s)
- Soroosh Sabeti
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Redouane Ternifi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Nicholas B. Larson
- Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Michael C. Olson
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Thomas D. Atwell
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Mostafa Fatemi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Azra Alizad
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- *Correspondence: Azra Alizad,
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Fraquelli M, Nadarevic T, Colli A, Manzotti C, Giljaca V, Miletic D, Štimac D, Casazza G. Contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 2022; 9:CD013483. [PMID: 36053210 PMCID: PMC9438628 DOI: 10.1002/14651858.cd013483.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer-related deaths. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha-foetoprotein, or both. According to guidelines, a single contrast-enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging. Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real-time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes. OBJECTIVES 1. To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting. 2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results. SEARCH METHODS We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021. SELECTION CRITERIA We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants. - CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence). - CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence). The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results. AUTHORS' CONCLUSIONS We found that by using CEUS, as an add-on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.
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Affiliation(s)
- Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy
| | - Cristina Manzotti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Vanja Giljaca
- Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham, UK
| | - Damir Miletic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health - Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Università degli Studi di Milano, Milan, Italy
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He M, Zhu L, Huang M, Zhong L, Ye Z, Jiang T. Comparison Between SonoVue and Sonazoid Contrast-Enhanced Ultrasound in Characterization of Focal Nodular Hyperplasia Smaller Than 3 cm. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:2095-2104. [PMID: 33305869 DOI: 10.1002/jum.15589] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVES This study aimed to compare the diagnostic efficacy of contrast-enhanced ultrasound (CEUS), including SonoVue (SV; sulfur hexafluoride; Bracco SpA, Milan, Italy) and Sonazoid (SZ; perflubutane; GE Healthcare, Oslo, Norway), and explore the differences between them in the characterization of CEUS features in focal nodular hyperplasia (FNH) smaller than 3 cm. METHODS This retrospective study included 31 lesions smaller than 3 cm diagnosed as FNH by CEUS between April 2019 and November 2019. Nine patients underwent SZ CEUS examinations, and 22 patients underwent SV CEUS examinations; all of them were confirmed by pathologic examinations or 2 other kinds of CEUS methods. We compared the CEUS features between SZ and SV in different phases, including arterial, portal venous, delayed, and Kupffer (SZ) phases. RESULTS Twenty-eight lesions were eventually diagnosed as FNH; 3 were misdiagnosed as FNH by SV CEUS. The overall diagnostic accuracy of CEUS including SZ and SV was 90.3% (28 of 31). No significant difference was found (P > .05) for the positive predictive value. Likewise, no significant difference in depicting centrifugal filling (9 of 9 versus 19 of 19), spoke wheel artery (6 of 9 versus 8 of 19), or feeding artery (2 of 9 versus 10 of 19) features was found between the contrast agents; However, SZ was significantly better at depicting the presence of a central scar than SV (5 of 9 versus 3 of 19; P = .030). Misdiagnosed cases are discussed in detail. CONCLUSIONS Contrast-enhanced ultrasound enables an accurate diagnosis in FNH smaller than 3 cm. Sonazoid CEUS and SV CEUS were comparable in diagnosing small FNH, and both agents were highly capable of depicting the centrifugal filling dynamic process of FNH smaller than 3 cm. Sonazoid CEUS might be better than SV CEUS at depicting a central scar.
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Affiliation(s)
- Mengna He
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lu Zhu
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Min Huang
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liyun Zhong
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhengdu Ye
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian'an Jiang
- Department of Ultrasound, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Xuan Z, Wu N, Li C, Liu Y. Application of contrast-enhanced ultrasound in the pathological grading and prognosis prediction of hepatocellular carcinoma. Transl Cancer Res 2021; 10:4106-4115. [PMID: 35116708 PMCID: PMC8799228 DOI: 10.21037/tcr-21-1264] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/10/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND To explore the clinical application value of contrast-enhanced ultrasound (CEUS) in the pathological grading and prognosis prediction of hepatocellular carcinoma (HCC). METHODS A retrospective analysis was performed of 128 patients with primary HCC who underwent CEUS examination in our hospital from January 2017 to June 2020. Patients were divided into three groups: highly-differentiated group, moderately-differentiated group, and poorly-differentiated group. Quantitative analysis of the relationships between the rise time (RT), time to peak (TTP), mean transit time (mTT), intensity maximum (Imax), enhancement rate, and pathological grade of CEUS was performed. In addition, the follow-up patients were divided into a recurrence group and non-recurrence group, and the relationships between RT, TTP, mTT, Imax, and enhancement rate of CEUS were analyzed. RESULTS Among the 128 patients, 23 were highly-differentiated, 63 were moderately-differentiated, and 42 were poorly-differentiated. In addition, there were 31 patients in the recurrence group and 97 patients in the non-recurrence group. RT, TTP, and enhancement rate had significant differences in the highly-differentiated, moderately-differentiated, and poorly-differentiated groups. At the same time, RT and TTP were positively correlated with the differentiation degree, while the enhancement rate was negatively correlated with the differentiation degree. Furthermore, RT, TTP, and enhancement rate were statistically significant for the diagnosis of HCC with high, moderate, and poor differentiation, among which RT had the highest diagnostic accuracy. In the recurrence group, RT, TTP, and Imax were lower than those in the non-recurrence group, and the enhancement rate was greater than that in the non-recurrence group. Moreover, low levels of RT, TTP, and Imax along with positive microvascular invasion (MVI) and poor differentiation were risk factors for HCC recurrence, and there was no significant relationship between the average tumor diameter and HCC recurrence. CONCLUSIONS CEUS can significantly show the differences between the RT, TTP, and enhancement rate of HCC across different levels of differentiation. It can also predict whether the disease will relapse. Moreover, low levels of RT, TTP, and Imax as well as positive MVI and poor differentiation can cause the recurrence of HCC.
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Affiliation(s)
- Zhidong Xuan
- Ultrasound Three Department, Cangzhou Central Hospital, Cangzhou, China
| | - Na Wu
- Ultrasound Three Department, Cangzhou Central Hospital, Cangzhou, China
| | - Chao Li
- Ultrasound Three Department, Cangzhou Central Hospital, Cangzhou, China
| | - Yongrong Liu
- Ultrasound Three Department, Cangzhou Central Hospital, Cangzhou, China
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10
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Li W, Lv XZ, Zheng X, Ruan SM, Hu HT, Chen LD, Huang Y, Li X, Zhang CQ, Xie XY, Kuang M, Lu MD, Zhuang BW, Wang W. Machine Learning-Based Ultrasomics Improves the Diagnostic Performance in Differentiating Focal Nodular Hyperplasia and Atypical Hepatocellular Carcinoma. Front Oncol 2021; 11:544979. [PMID: 33842303 PMCID: PMC8033198 DOI: 10.3389/fonc.2021.544979] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 03/03/2021] [Indexed: 12/12/2022] Open
Abstract
Background The typical enhancement patterns of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) are hyper-enhanced in the arterial phase and washed out during the portal venous and late phases. However, atypical variations make a differential diagnosis both challenging and crucial. We aimed to investigate whether machine learning-based ultrasonic signatures derived from CEUS images could improve the diagnostic performance in differentiating focal nodular hyperplasia (FNH) and atypical hepatocellular carcinoma (aHCC). Patients and Methods A total of 226 focal liver lesions, including 107 aHCC and 119 FNH lesions, examined by CEUS were reviewed retrospectively. For machine learning-based ultrasomics, 3,132 features were extracted from the images of the baseline, arterial, and portal phases. An ultrasomics signature was generated by a machine learning model. The predictive model was constructed using the support vector machine method trained with the following groups: ultrasomics features, radiologist’s score, and combination of ultrasomics features and radiologist’s score. The diagnostic performance was explored using the area under the receiver operating characteristic curve (AUC). Results A total of 14 ultrasomics features were chosen to build an ultrasomics model, and they presented good performance in differentiating FNH and aHCC with an AUC of 0.86 (95% confidence interval [CI]: 0.80, 0.89), a sensitivity of 76.6% (95% CI: 67.5%, 84.3%), and a specificity of 80.5% (95% CI: 70.6%, 85.9%). The model trained with a combination of ultrasomics features and the radiologist’s score achieved a significantly higher AUC (0.93, 95% CI: 0.89, 0.96) than that trained with the radiologist’s score (AUC: 0.84, 95% CI: 0.79, 0.89, P < 0.001). For the sub-group of HCC with normal AFP value, the model trained with a combination of ultrasomics features, and the radiologist’s score remain achieved the highest AUC of 0.92 (95% CI: 0.87, 0.96) compared to that with the ultrasomics features (AUC: 0.86, 95% CI: 0.74, 0.89, P < 0.001) and radiologist’s score (AUC: 0.86, 95% CI: 0.79, 0.91, P < 0.001). Conclusions Machine learning-based ultrasomics performs as well as the staff radiologist in predicting the differential diagnosis of FNH and aHCC. Incorporating an ultrasomics signature into the radiologist’s score improves the diagnostic performance in differentiating FNH and aHCC.
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Affiliation(s)
- Wei Li
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Zhou Lv
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin Zheng
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Si-Min Ruan
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hang-Tong Hu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yang Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xin Li
- Research Center, GE Healthcare, Shanghai, China
| | - Chu-Qing Zhang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.,Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Bo-Wen Zhuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, Ultrasomics Artificial Intelligence X-Lab, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Lupsor-Platon M, Serban T, Silion AI, Tirpe GR, Tirpe A, Florea M. Performance of Ultrasound Techniques and the Potential of Artificial Intelligence in the Evaluation of Hepatocellular Carcinoma and Non-Alcoholic Fatty Liver Disease. Cancers (Basel) 2021; 13:790. [PMID: 33672827 PMCID: PMC7918928 DOI: 10.3390/cancers13040790] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/14/2020] [Accepted: 02/09/2021] [Indexed: 12/12/2022] Open
Abstract
Global statistics show an increasing percentage of patients that develop non-alcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma (HCC), even in the absence of cirrhosis. In the present review, we analyzed the diagnostic performance of ultrasonography (US) in the non-invasive evaluation of NAFLD and NAFLD-related HCC, as well as possibilities of optimizing US diagnosis with the help of artificial intelligence (AI) assistance. To date, US is the first-line examination recommended in the screening of patients with clinical suspicion of NAFLD, as it is readily available and leads to a better disease-specific surveillance. However, the conventional US presents limitations that significantly hamper its applicability in quantifying NAFLD and accurately characterizing a given focal liver lesion (FLL). Ultrasound contrast agents (UCAs) are an essential add-on to the conventional B-mode US and to the Doppler US that further empower this method, allowing the evaluation of the enhancement properties and the vascular architecture of FLLs, in comparison to the background parenchyma. The current paper also explores the new universe of AI and the various implications of deep learning algorithms in the evaluation of NAFLD and NAFLD-related HCC through US methods, concluding that it could potentially be a game changer for patient care.
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Affiliation(s)
- Monica Lupsor-Platon
- Medical Imaging Department, Regional Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.S.); (A.I.S.)
| | - Alexandra Iulia Silion
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.S.); (A.I.S.)
| | - George Razvan Tirpe
- County Emergency Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400000 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Mira Florea
- Community Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400001 Cluj-Napoca, Romania;
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12
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Contrast-Enhanced Ultrasound for Focal Hepatic Lesions: When to Use and How to Differentiate Lesions? Ultrasound Q 2020; 36:224-234. [PMID: 32890325 DOI: 10.1097/ruq.0000000000000475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Contrast-enhanced ultrasound can be used effectively to evaluate focal hepatic lesions and offers unique advantages over computed tomography and magnetic resonance imaging. Serial vascular filling patterns of focal hepatic lesions during arterial, portal, and late phases can provide unique information on lesion characterization and differentiation. Sensitive depiction of arterial hypervascularity and analysis of washout pattern are clues for differentiation of several indeterminate hepatic nodules on conventional ultrasound and computed tomography/magnetic resonance. In this report, we present cases demonstrating clinical applications of contrast-enhanced ultrasound in the diagnosis and management of focal hepatic lesions.
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Fan PL, Xia HS, Ding H, Dong Y, Chen LL, Wang WP. Characterization of Early Hepatocellular Carcinoma and High-Grade Dysplastic Nodules on Contrast-Enhanced Ultrasound: Correlation With Histopathologic Findings. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2020; 39:1799-1808. [PMID: 32378794 DOI: 10.1002/jum.15288] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/13/2020] [Accepted: 03/17/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVES To explore the enhancement features of early hepatocellular carcinoma (HCC, including well-differentiated HCC and high-grade dysplastic nodules with a focus of HCC) and high-grade dysplastic nodules (HGDNs) on contrast-enhanced ultrasound (CEUS), correlated with the histopathologic findings. METHODS This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings. RESULTS Thirty-eight (55.1%) early HCCs showed arterial-phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late-phase wash-out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash-out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very-late wash-out (>120 seconds). Wash-out was not observed in all HGDNs. Of the 16 HGDNs, arterial-phase isoenhancement without portal venous/late-phase wash-out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial-phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039). CONCLUSIONS Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.
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Affiliation(s)
- Pei-Li Fan
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, China
| | - Han-Sheng Xia
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, China
| | - Hong Ding
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, China
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, China
| | - Ling-Li Chen
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai Institute of Medical Imaging, Shanghai, China
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14
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Duan Y, Xie X, Li Q, Mercaldo N, Samir AE, Kuang M, Lin M. Differentiation of regenerative nodule, dysplastic nodule, and small hepatocellular carcinoma in cirrhotic patients: a contrast-enhanced ultrasound-based multivariable model analysis. Eur Radiol 2020; 30:4741-4751. [PMID: 32307563 DOI: 10.1007/s00330-020-06834-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 03/03/2020] [Accepted: 03/25/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To develop a contrast-enhanced ultrasound (CEUS)-based model for differentiating cirrhotic liver lesions and for active surveillance of hepatocellular carcinoma (HCC). METHODS Patients with focal liver lesions (FLLs) with biopsy/resection-proven pathology and pre-procedure CEUS were enrolled from our institution between January 2011 and November 2014. Univariable and multivariable regression models were constructed using qualitative CEUS features and/or contrast arrival time ratio (CATR). The optimism-adjusted Harrell's generalized concordance index (CH) was used to quantify the discriminatory ability of each CEUS feature and model. RESULTS A total of 149 patients (113 men and 36 women) with 162 FLLs were enrolled with mean age 53.4 ± 12.7 years. A 0.1-unit reduction in CATR was associated with a 68% increase in the odds of having a higher nodule ranking (RN < DN < small HCC) (OR, 0.32; 95% CI, 0.20-0.50, p < .001). Arterial phase hypoenhancement and isoenhancement were inversely associated with a higher nodule ranking compared to hyperenhancement. Late-phase isoenhancement was associated with lower odds of a higher nodule ranking. The CEUS + CATR model (CH 0.92, 0.89-0.95) provided greater discriminatory ability when compared to the CATR model (ΔCH 0.09, 0.04-0.13, p < .001) and the CEUS model (ΔCH 0.03, 0.01-0.05, p = .02). CONCLUSIONS Our results provide preliminary evidence that multivariable regression model constructed using both qualitative CEUS features and CATR provides the greatest discriminatory ability to differentiate RN, DN, and small HCC in patients with cirrhosis, and might allow for active surveillance of the progression of cirrhotic liver lesions. KEY POINTS • Proportional odds logistic regression models based on qualitative CEUS features and/or CATR can be used for differentiating cirrhotic liver lesions and for active surveillance of HCC. • The reduction of CATR (RN < DN < small HCC) was strongly associated with high-risk cirrhotic liver nodules. • Inclusion of CATR in the CEUS prediction model significantly improved its performance for cirrhotic liver lesions risk-stratification.
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Affiliation(s)
- Yu Duan
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Qian Li
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA
| | - Nathaniel Mercaldo
- Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, 101 Merrimac Street, Suite 1010, Boston, MA, 02114, USA
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA
| | - Ming Kuang
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Manxia Lin
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
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15
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Mai B, Wang X, Liu Q, Zhang K, Wang P. The Application of DVDMS as a Sensitizing Agent for Sono-/Photo-Therapy. Front Pharmacol 2020; 11:19. [PMID: 32116698 PMCID: PMC7020569 DOI: 10.3389/fphar.2020.00019] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 01/08/2020] [Indexed: 01/01/2023] Open
Abstract
Both photodynamic therapy (PDT) and sonodynamic therapy (SDT) are fast growing activated therapies by using light or ultrasound to initiate catalytic reaction of sensitizing agents, showing great potentials in clinics because of high safety and noninvasiveness. Sensitizers are critical components in PDT and SDT. Sinoporphyrin sodium (DVDMS) is an effective constituent derived from Photofrin that has been approved by FDA. This review is based on previous articles that explore the applications of DVDMS mediated photodynamic/sonodynamic cancer therapy and antimicrobial chemotherapy. Researchers utilize different cell lines, distinct treatment protocols to explore the enhanced therapeutic response of neoplastic lesion. Moreover, by designing a series of nanoparticles for loading DVDMS to improve the cellular uptake and antitumor efficacy of PDT/SDT, which integrates diagnostics into therapeutics for precision medical applications. During the sono-/photo-activated process, the balance between oxidation and antioxidation, numerous signal transduction and cell death pathways are also involved. In addition, DVDMS mediated photodynamic antimicrobial chemotherapy (PACT) can effectively suppress bacteria and multidrug resistant bacteria proliferation, promote the healing of wounds in burn infection. In brief, these efficient preclinical studies indicate a good promise for DVDMS application in the activated sono-/photo-therapy.
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Affiliation(s)
- Bingjie Mai
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Xiaobing Wang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Quanhong Liu
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Kun Zhang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Pan Wang
- National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, China
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Hou R, Liang X, Li X, Zhang X, Ma X, Wang F. In situconversion of rose bengal microbubbles into nanoparticles for ultrasound imaging guided sonodynamic therapy with enhanced antitumor efficacy. Biomater Sci 2020; 8:2526-2536. [DOI: 10.1039/c9bm02046b] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Sonosensitizer microbubbles enhance drug accumulation and the antitumor efficacy of sonodynamic therapy by ultrasound mediated micro to nano conversion.
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Affiliation(s)
- Rui Hou
- Medical Isotopes Research Center and Department of Radiation Medicine
- School of Basic Medical Sciences
- Peking University
- Beijing
- China
| | - Xiaolong Liang
- Department of Ultrasound
- Peking University Third Hospital
- Beijing
- China
| | - Xiaoda Li
- Medical Isotopes Research Center and Department of Radiation Medicine
- School of Basic Medical Sciences
- Peking University
- Beijing
- China
| | - Xu Zhang
- Medical Isotopes Research Center and Department of Radiation Medicine
- School of Basic Medical Sciences
- Peking University
- Beijing
- China
| | - Xiaotu Ma
- Key Laboratory of Protein and Peptide Pharmaceuticals
- CAS Center for Excellence in Biomacromolecules
- Institute of Biophysics
- Chinese Academy of Sciences
- Beijing
| | - Fan Wang
- Medical Isotopes Research Center and Department of Radiation Medicine
- School of Basic Medical Sciences
- Peking University
- Beijing
- China
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17
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Chen S, Xu XL, Zhou B, Tian J, Luo BM, Zhang LM. Acidic pH-Activated Gas-Generating Nanoparticles with Pullulan Decorating for Hepatoma-Targeted Ultrasound Imaging. ACS APPLIED MATERIALS & INTERFACES 2019; 11:22194-22205. [PMID: 31199110 DOI: 10.1021/acsami.9b06745] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Contrast-enhanced ultrasound (US) is a widely used imaging modality for hepatocellular carcinoma diagnosis. Mostly, US imaging is confined to the intravascular process because of the limitation of the microbubble contrast agent currently utilized. Targeted contrast agents that incline to accumulate in tumor tissue or tumor cells and enhance the US signal may advance the sensitivity of ultrasonography and exploit the dimension of US imaging of tumor at the molecular level. In this study, we developed CaCO3/pul-PCB (CPP) hybrid nanoparticles with hepatoma-targeting pullulan decorating on the surface through a mineralization route using the pullulan- graft-poly(carboxybetaine methacrylate) (pul-PCB) copolymer as a modifier. This particle was stable in blood physiological pH and generated echogenic CO2 bubbles under tumoral acidic conditions, which enabled the US signal enhancement. Upon intravenous injection, CPP hybrid nanoparticles accumulated efficiently in tumor tissue and exhibited sixfold contrast enhancement in 35 min at the tumor site in the hepatoma-bearing mice model. By contrast, there was barely any signal change in normal liver tissue. Therefore, the presented CPP hybrid nanoparticle is a promising contrast agent for effective US imaging of hepatoma.
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Affiliation(s)
- Shanshan Chen
- DSAPM Lab and PCFM Lab, School of Materials Science and Engineering , Sun Yat-sen University , Guangzhou 510275 , China
| | - Xiao-Lin Xu
- Department of Ultrasound, Sun Yat-sen Memorial Hospital , Sun Yat-sen University , Guangzhou 510120 , China
| | - Boyang Zhou
- Department of Ultrasound, Sun Yat-sen Memorial Hospital , Sun Yat-sen University , Guangzhou 510120 , China
| | - Jing Tian
- Department of Ultrasound, Sun Yat-sen Memorial Hospital , Sun Yat-sen University , Guangzhou 510120 , China
| | - Bao-Ming Luo
- Department of Ultrasound, Sun Yat-sen Memorial Hospital , Sun Yat-sen University , Guangzhou 510120 , China
| | - Li-Ming Zhang
- DSAPM Lab and PCFM Lab, School of Materials Science and Engineering , Sun Yat-sen University , Guangzhou 510275 , China
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Yang HK, Burns PN, Jang HJ, Kono Y, Khalili K, Wilson SR, Kim TK. Contrast-enhanced ultrasound approach to the diagnosis of focal liver lesions: the importance of washout. Ultrasonography 2019; 38:289-301. [PMID: 31311068 PMCID: PMC6769186 DOI: 10.14366/usg.19006] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 03/17/2019] [Indexed: 12/12/2022] Open
Abstract
Contrast-enhanced ultrasound (CEUS) is a powerful technique for differentiating focal liver lesions (FLLs) without the risks of potential nephrotoxicity or ionizing radiation. In the diagnostic algorithm for FLLs on CEUS, washout is an important feature, as its presence is highly suggestive of malignancy and its characteristics are useful in distinguishing hepatocellular from nonhepatocellular malignancies. Interpreting washout on CEUS requires an understanding that microbubble contrast agents are strictly intravascular, unlike computed tomography or magnetic resonance imaging contrast agents. This review explains the definition and types of washout on CEUS in accordance with the 2017 version of the CEUS Liver Imaging Reporting and Data System and presents their applications to differential diagnosis with illustrative examples. Additionally, we propose potential mechanisms of rapid washout and describe the washout phenomenon in benign entities.
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Affiliation(s)
- Hyun Kyung Yang
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Peter N Burns
- Department of Medical Biophysics, Sunnybrook Research Institute, University of Toronto, Toronto, Canada
| | - Hyun-Jung Jang
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Yuko Kono
- Departments of Medicine and Radiology, University of California, San Diego, CA, USA
| | - Korosh Khalili
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
| | - Stephanie R Wilson
- Diagnostic Imaging, Department of Radiology, University of Calgary, Calgary, Canada
| | - Tae Kyoung Kim
- Joint Department of Medical Imaging, University of Toronto, Toronto, Canada
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Bai M, Dong Y, Huang H, Fu H, Duan Y, Wang Q, Du L. Tumour targeted contrast enhanced ultrasound imaging dual-modal microbubbles for diagnosis and treatment of triple negative breast cancer. RSC Adv 2019; 9:5682-5691. [PMID: 35515929 PMCID: PMC9060891 DOI: 10.1039/c8ra09737b] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 02/02/2019] [Indexed: 01/17/2023] Open
Abstract
At present, the treatment of triple negative breast cancer (TNBC) is a worldwide problem, urgently requiring early precise diagnosis and effective treatment methods. In our study, we designed a type of tumour targeted dual-modal microbubbles, paclitaxel (PTX)-loaded RGD-lipid microbubbles (PTX@RGD-MBs), combined with ultrasonic targeted microbubble destruction (UTMD) to precisely diagnose TNBC and to improve the curative effect. As the first-line drug, PTX, lacking specific tumour targeting and the ability to be effectively internalized by TNBC cells, is still not effective in killing TNBC cells. For this reason, we used the tumour active targeting peptide RGD to precisely guide MBs around TNBC cells through the high affinity to the integrin αvβ3 receptor, and use UTMD to generate shear stress on cells to open transient pores in the cellular membrane, so as to improve MB penetration into the cellular membrane. Sulfur hexafluoride (SF6) as the internal gas of MBs can greatly improve the resolution and sensitivity of conventional US images through nonlinear harmonics to enhance the comparison between lesions and surrounding normal tissues. The results in our study demonstrated that RGD-MBs with UTMD were internalized by TNBC cells more effectively, leading to significant increase in intercellular drug concentrations of TNBC cells, thus achieving the best inhibitory effect on TNBC cells in vitro. Ultrasonic experiment showed that PTX@RGD-MBs produced high quality contrast enhanced ultrasound (CEUS) images in vitro and in vivo, providing a better method for diagnosis and evaluation of the TNBC. Therefore, we conclude the advantages of excellent anti-tumour effect and CEUS imaging of PTX@RGD-MBs provided a better application for diagnosis and treatment of TNBC. Tumour targeted contrast-enhanced ultrasound imaging dual-modal microbubbles (PTX@RGD-MBs) combined with UTMD for diagnosing and treating triple negative breast cancer.![]()
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Affiliation(s)
- Min Bai
- Department of Ultrasound
- Shanghai General Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai 200080
- China
| | - Yang Dong
- State Key Laboratory of Oncogenes and Related Genes
- Shanghai Cancer Institute
- Renji Hospital
- School of Medicine
- Shanghai Jiao Tong University
| | - Hui Huang
- State Key Laboratory of Oncogenes and Related Genes
- Shanghai Cancer Institute
- Renji Hospital
- School of Medicine
- Shanghai Jiao Tong University
| | - Hao Fu
- State Key Laboratory of Oncogenes and Related Genes
- Shanghai Cancer Institute
- Renji Hospital
- School of Medicine
- Shanghai Jiao Tong University
| | - Yourong Duan
- State Key Laboratory of Oncogenes and Related Genes
- Shanghai Cancer Institute
- Renji Hospital
- School of Medicine
- Shanghai Jiao Tong University
| | - Qi Wang
- Key Laboratory for Advanced Materials and Institute of Fine Chemicals
- Shanghai Key Laboratory of Functional Materials Chemistry
- School of Chemistry and Molecular Engineering
- East China University of Science and Technology
- Shanghai 200237
| | - Lianfang Du
- Department of Ultrasound
- Shanghai General Hospital
- Shanghai Jiao Tong University School of Medicine
- Shanghai 200080
- China
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Shin SK, Choi DJ, Kim JH, Kim YS, Kwon OS. Characteristics of contrast-enhanced ultrasound in distinguishing small (≤3 cm) hepatocellular carcinoma from intrahepatic cholangiocarcinoma. Medicine (Baltimore) 2018; 97:e12781. [PMID: 30313099 PMCID: PMC6203535 DOI: 10.1097/md.0000000000012781] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Contrast-enhanced ultrasound (CEUS) is highly accurate in depicting the vascularity of liver nodules. The aim of this study was to verify the characteristics of CEUS in distinguishing small (≤3 cm) hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC).A total of 65 patients with a liver nodule (HCC, n = 58; ICC, n = 7) smaller than 3 cm who underwent liver CEUS and pathologic confirmation were retrospectively reviewed. CEUS findings were compared with histopathologic and clinical data.Arterial-phase hyperenhancement and portal-delayed-phase wash-out on CEUS were observed in 77.6% (45/58) of HCCs and 85.7% (6/7) of ICCs. Time of arterial-phase hyperenhancement (11 seconds [6-20] vs 16 seconds [14-19], P = .008), time of portal-delayed-phase wash-out (65 seconds (15-260) vs 35 secconds (27-54), P = .002), and time interval between arterial-phase hyperenhancement and portal-delayed-phase wash-out (50 seconds [5-249] vs 19 seconds [13-35], P < .001) on CEUS were significantly different between HCCs and ICCs showing arterial-phase hyperenhancement and portal-delayed-phase wash-out. The sensitivity, specificity, positive predictive value, and negative predictive value of time interval more than 25 seconds between arterial-phase hyperenhancement and portal-delayed-phase wash-out on CEUS for the differentiation of HCCs and ICCs were 91.1%, 83.3%, 97.6%, and 55.6%, respectively.The time interval between arterial-phase hyperenhancement and portal-delayed-phase wash-out on CEUS was the most sensitive indicator in distinguishing small HCC from ICC showing arterial-phase hyperenhancement and portal-delayed-phase wash-out.
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21
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Ranganath PG, Robbin ML, Back SJ, Grant EG, Fetzer DT. Practical advantages of contrast-enhanced ultrasound in abdominopelvic radiology. Abdom Radiol (NY) 2018; 43:998-1012. [PMID: 29332247 DOI: 10.1007/s00261-017-1442-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Computed tomography (CT) and magnetic resonance imaging (MRI) are two of the workhorse modalities of abdominopelvic radiology. However, these modalities are not without patient- and technique-specific limitations that may prevent a timely and accurate diagnosis. Contrast-enhanced ultrasound (CEUS) is an effective, rapid, and cost-effective imaging modality with expanding clinical utility in the United States. In this pictorial essay, we provide a case-based discussion demonstrating the practical advantages of CEUS in evaluating a variety of pathologies in which CT or MRI was precluded or insufficient. Through these advantages, CEUS can serve a complementary role with CT and MRI in comprehensive abdominopelvic radiology.
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Yang D, Li R, Zhang XH, Tang CL, Ma KS, Guo DY, Yan XC. Perfusion Characteristics of Hepatocellular Carcinoma at Contrast-enhanced Ultrasound: Influence of the Cellular differentiation, the Tumor Size and the Underlying Hepatic Condition. Sci Rep 2018; 8:4713. [PMID: 29549368 PMCID: PMC5856788 DOI: 10.1038/s41598-018-23007-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 03/05/2018] [Indexed: 12/12/2022] Open
Abstract
This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.
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Affiliation(s)
- Dan Yang
- Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - Rui Li
- Department Ultrasound, the Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Xiao-Hang Zhang
- Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - Chun-Lin Tang
- Department Ultrasound, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - Kuan-Sheng Ma
- Department Hepato-biliary-Pancreatic Surgery, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - De-Yu Guo
- Department Pathology, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
| | - Xiao-Chu Yan
- Department Pathology, Southwest Hospital Affiliated to Third Military Medical University, Chongqing, China
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23
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Guo S, Xu P, Zhou A, Wang G, Chen W, Mei J, Xiao F, Liu J, Zhang C. Contrast-Enhanced Ultrasound Differentiation Between Low- and High- Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2017; 36:2287-2297. [PMID: 28556470 DOI: 10.1002/jum.14262] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 02/09/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVES Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). METHODS The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. RESULTS Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). CONCLUSIONS Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis.
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Affiliation(s)
- Suping Guo
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Pan Xu
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Aiyun Zhou
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Gongxian Wang
- Department of Urology Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Weimin Chen
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jinhong Mei
- Department of Pathology, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fan Xiao
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Juan Liu
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Cheng Zhang
- Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China
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Xie R, Xu T, Zhu J, Wei X, Zhu W, Li L, Wang Y, Han Y, Zhou J, Bai Y. The Combination of Glycolytic Inhibitor 2-Deoxyglucose and Microbubbles Increases the Effect of 5-Aminolevulinic Acid-Sonodynamic Therapy in Liver Cancer Cells. ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:2640-2650. [PMID: 28843620 DOI: 10.1016/j.ultrasmedbio.2017.06.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 06/16/2017] [Accepted: 06/29/2017] [Indexed: 06/07/2023]
Abstract
Sonodynamic therapy (SDT) overcomes the shortcoming of photodynamic therapy in the treatment of cancer. Previous studies indicated that the glycolysis inhibitor 2-deoxyglucose (2-DG) potentiated photodynamic therapy induced tumor cell death and microbubbles (MBs) improved the SDT performance. We hypothesized that the combination of 2-DG and MBs will increase the effect of 5-aminolevulinic acid (ALA)-SDT in HepG2 liver cancer cells. When cells were treated with 5-min ALA-SDT and 2-mmol/L 2-DG, the cell survival rate decreased to 73.0 ± 7.1% and 75.2 ± 7.9%, respectively. Furthermore, 2 mmol/L 2-DG increased 5-min ALA-SDT induced growth inhibition and augmented ALA-SDT induced cell apoptotic rate from 9.8 ± 0.7% to 17.4 ± 2.2%. In the combination group (2-DG and ALA-SDT group), HepG2 cells possessed typical apoptotic characters. 2-DG also increased ALA-SDT associated intracellular reactive oxygen species generation and loss of mitochondrial membrane potential. Moreover, SonoVue MBs had stimulatory function on cell viability inhibition, apoptosis, reactive oxygen species production and mitochondrial membrane potential loss for combination treatment. This study suggests a promising therapeutic strategy using a combination of 2-DG, MBs and ALA-SDT for treating liver cancer.
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Affiliation(s)
- Rui Xie
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Tongying Xu
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jiuxin Zhu
- Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China
| | - Xiaoli Wei
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wenting Zhu
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Longmin Li
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yufeng Wang
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yu Han
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jianhua Zhou
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuxian Bai
- Department of Digestive Internal Medicine & Photodynamic Therapy Center, Harbin Medical University Cancer Hospital, Harbin, China.
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25
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Shi D, Guo L, Duan S, Shang M, Meng D, Cheng L, Li J. Influence of tumor cell lines derived from different tissue on sonoporation efficiency under ultrasound microbubble treatment. ULTRASONICS SONOCHEMISTRY 2017; 38:598-603. [PMID: 27562907 DOI: 10.1016/j.ultsonch.2016.08.022] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 08/14/2016] [Accepted: 08/15/2016] [Indexed: 06/06/2023]
Abstract
To reveal the effect of tumor cell lines derived from different tissue on sonoporation efficiency under ultrasound microbubble (USMB) treatment, and meanwhile to determine the optimum parameter combination for each tumor cell line. Human breast tumor (MCF-7), ovarian tumor (A2780), liver tumor (Bel7402) and thyroid tumor (ARO) were exposed to ultrasound in the presence of SonoVue MBs. The major parameters for the designed experiments including MB concentration (A1:10%, A2:20%, A3:30%), sound intensity (B1:0.5, B2:1.0, B3:1.5W/cm2), irradiation time (C1:30, C2:60, C3:90s). An orthogonal array experimental design based on three levels L9 (33) of the above three parameters was employed to optimize the sonoporation efficiency. MTT experiment was used to calculate cell survival rate. FD500 uptake assay and cytometry were performed to evaluate transference percentage. The optimum parameter combination for each tumor cell line was different (MCF-7: A3B1C1, A2780: A1B3C3, Bel7402: A2B3C2, ARO: A2B3C2). Under their own optimum parameter combination, four kinds of tumor cell line exhibited different optimum sonoporation efficiency (MCF-7: 55.05±5.29%; A2780: 45.62±7.35%; Bel7402: 39.37±4.11%; ARO: 53.37±3.94%). Multiple comparison with LSD-t test showed that the sonoporation efficiency between four kinds of cell line was statistically significant (P<0.05), with the exception of MCF-7 VS. ARO (P=0.487). Tumor cell lines derived from different tissue can impact the sonoporation efficiency, and optimizing the exposure parameters can safely and efficiently increase the cell membrane permeability.
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Affiliation(s)
- Dandan Shi
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Lu Guo
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Sujuan Duan
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Mengmeng Shang
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Dong Meng
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Lin Cheng
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China
| | - Jie Li
- Department of Ultrasound, Qilu Hospital, Shandong University, Jinan 250012, China.
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Burrowes DP, Medellin A, Harris AC, Milot L, Wilson SR. Contrast-enhanced US Approach to the Diagnosis of Focal Liver Masses. Radiographics 2017; 37:1388-1400. [DOI: 10.1148/rg.2017170034] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- David P. Burrowes
- From the Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B., A.M., S.R.W.); Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada (A.C.H.); and Department of Radiology, University of Toronto, Toronto, Ontario, Canada (L.M.). Recipient of a Magna Cum Laude award for an education exhibit at the 2016 RSNA Annual Meeting
| | - Alexandra Medellin
- From the Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B., A.M., S.R.W.); Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada (A.C.H.); and Department of Radiology, University of Toronto, Toronto, Ontario, Canada (L.M.). Recipient of a Magna Cum Laude award for an education exhibit at the 2016 RSNA Annual Meeting
| | - Allison C. Harris
- From the Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B., A.M., S.R.W.); Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada (A.C.H.); and Department of Radiology, University of Toronto, Toronto, Ontario, Canada (L.M.). Recipient of a Magna Cum Laude award for an education exhibit at the 2016 RSNA Annual Meeting
| | - Laurent Milot
- From the Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B., A.M., S.R.W.); Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada (A.C.H.); and Department of Radiology, University of Toronto, Toronto, Ontario, Canada (L.M.). Recipient of a Magna Cum Laude award for an education exhibit at the 2016 RSNA Annual Meeting
| | - Stephanie R. Wilson
- From the Department of Radiology, University of Calgary, Calgary, Alberta, Canada (D.P.B., A.M., S.R.W.); Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada (A.C.H.); and Department of Radiology, University of Toronto, Toronto, Ontario, Canada (L.M.). Recipient of a Magna Cum Laude award for an education exhibit at the 2016 RSNA Annual Meeting
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27
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Zhu W, Qing X, Yan F, Luo Y, Li Y, Zhou X. Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict Microvascular Invasion in Hepatocellular Carcinoma? ULTRASOUND IN MEDICINE & BIOLOGY 2017; 43:1571-1580. [PMID: 28502665 DOI: 10.1016/j.ultrasmedbio.2017.04.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 03/31/2017] [Accepted: 04/04/2017] [Indexed: 06/07/2023]
Abstract
The objective of this study was to investigate use of the washout rate of hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative determination of the presence of microvascular invasion. The study included 271 patients who underwent liver resection for hepatocellular carcinoma between April 2008 and December 2012, and were examined with contrast-enhanced ultrasound before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout patterns were classified according to the start time of washout: rapid, portal, delayed and slow. Rapid washout, presence of two or more tumors and tumor size ≥5 cm were identified as independent pre-operative predictors of microvascular invasion on multivariate analysis. Recurrence rates for patients with none, one, two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In combination with tumor number and tumor size, contrast-enhanced ultrasound washout rate may have a role in identifying hepatocellular carcinoma patients with microvascular invasion.
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Affiliation(s)
- Wei Zhu
- Echo Lab of Cardiology Department/Department of Ultrasound, West China Hospital, Chengdu, Sichuan, China
| | - Xiachuan Qing
- Department of Ultrasound, Nanchong Central Hospital, Nanchong, Sichuan, China
| | - Feng Yan
- Department of Ultrasound, West China Hospital, Chengdu, Sichuan, China
| | - Yan Luo
- Department of Ultrasound, West China Hospital, Chengdu, Sichuan, China
| | - Yongzhong Li
- Department of Ultrasound, West China Hospital, Chengdu, Sichuan, China
| | - Xiang Zhou
- Department of Ultrasound, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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28
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Shin SK, Kim YS, Choi SJ, Shim YS, Jung DH, Kwon OS, Choi DJ, Kim JH. Characterization of small (≤3 cm) hepatic lesions with atypical enhancement feature and hypointensity in hepatobiliary phase of gadoxetic acid-enhanced MRI in cirrhosis: A STARD-compliant article. Medicine (Baltimore) 2017; 96:e7278. [PMID: 28723741 PMCID: PMC5521881 DOI: 10.1097/md.0000000000007278] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
It is difficult to characterize the nodular lesions in cirrhotic liver if typical enhancement pattern is not present on dynamic contrast-enhanced imagings. Although the signal intensity of the hepatobiliary phase in gadoxetic acid-enhanced magnetic resonance imaging (MRI) is helpful for characterization of the lesions, some dysplastic nodules may also exhibit low signal intensity in the hepatobiliary phase. We aimed to assess the usefulness of gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI including diffusion-weighted imaging (DWI) for differentiation between atypical small hepatocellular carcinomas (HCCs) and dysplastic nodules showing low signal intensity (SI) in the hepatobiliary phase, and to evaluate the MRI findings in determining the histological grade of atypical HCCs in patients with cirrhosis.A total of 43 cirrhotic patients with a small (≤3 cm) liver nodule (n = 25, HCC; n = 18, dysplastic nodule) who underwent Gd-EOB-DTPA-enhanced MRI and pathologic confirmation were retrospectively reviewed. Atypical HCC was defined as not showing arterial hyperenhancement and delayed washout on dynamic MRI.High SI on both T2WI and DWI (sensitivity 80.0%, specificity 100%, positive predictive value 100%, negative predictive value 78.3%) was the most specific feature to differentiate atypical HCCs from dysplastic nodules. High SI on both T2WI and DWI (100% vs 61.5%, P = .039) or low SI on pre-enhanced T1WI (83.3% vs 30.8%, P = .021) was more frequent observed in Edmonson grade II-III HCCs compared with those in grade I HCCs.The combination of DWI and T2WI is most useful for the differentiation of atypical small HCCs from dysplastic nodules showing low SI in the hepatobiliary phase. Combination of DWI and T2WI or pre-enhanced T1WI seems to be useful for predicting the histological grade of atypical HCCs.
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Affiliation(s)
| | | | | | | | - Dong Hae Jung
- Department of Pathology, Gachon University Gil Medical Center, Incheon, Republic of Korea
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Terzi E, Salvatore V, Negrini G, Piscaglia F. Ongoing challenges in the diagnosis of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2016; 10:451-63. [PMID: 26603785 DOI: 10.1586/17474124.2016.1124758] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In 2001, the European Association for the Study of the Liver (EASL) endorsed the possibility of achieving a non-invasive diagnosis of Hepatocellular Carcinoma (HCC) for the first time. Since then, various refinements of the criteria and techniques capable of achieving this diagnosis and the role of plasma and tissue oncomarkers have been reported in the literature and have been accepted to different extents in various geographical areas. Such tools can also potentially imply prognostic significance. The present article critically discusses some of the most relevant and debated challenges which have emerged in this field, including the role of contrast-enhanced ultrasound, and of hepatocyte-specific magnetic resonance contrast agents, the pitfall of transient hepatic attenuation differences, the reliability of biopsy and the status of biomarkers.
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Affiliation(s)
- Eleonora Terzi
- a Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital , University of Bologna , Bologna , Italy
| | - Veronica Salvatore
- a Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital , University of Bologna , Bologna , Italy
| | - Giulia Negrini
- a Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital , University of Bologna , Bologna , Italy
| | - Fabio Piscaglia
- a Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, Sant'Orsola-Malpighi Hospital , University of Bologna , Bologna , Italy
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30
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Qian X, Zheng Y, Chen Y. Micro/Nanoparticle-Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2016; 28:8097-8129. [PMID: 27384408 DOI: 10.1002/adma.201602012] [Citation(s) in RCA: 543] [Impact Index Per Article: 60.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 05/28/2016] [Indexed: 05/08/2023]
Abstract
The fast development of photoactivation for cancer treatment provides an efficient photo-therapeutic strategy for cancer treatment, but traditional photodynamic or photothermal therapy suffers from the critical issue of low in vivo penetration depth of tissues. As a non-invasive therapeutic modality, sonodynamic therapy (SDT) can break the depth barrier of photoactivation because ultrasound has an intrinsically high tissue-penetration performance. Micro/nanoparticles can efficiently augment the SDT efficiency based on nanobiotechnology. The state-of-art of the representative achievements on micro/nanoparticle-enhanced SDT is summarized, and specific functions of micro/nanoparticles for SDT are discussed, from the different viewpoints of ultrasound medicine, material science and nanobiotechnology. Emphasis is put on the relationship of structure/composition-SDT performance of micro/nanoparticle-based sonosensitizers. Three types of micro/nanoparticle-augmented SDT are discussed, including organic and inorganic sonosensitizers and micro/nanoparticle-based but sonosensitizer-free strategies to enhance the SDT outcome. SDT-based synergistic cancer therapy augmented by micro/nanoparticles and their biosafety are also included. Some urgent critical issues and potential developments of micro/nanoparticle-augmented SDT for efficient cancer treatment are addressed. It is highly expected that micro/nanoparticle-augmented SDT will be quickly developed as a new and efficient therapeutic modality which will find practical applications in cancer treatment. At the same time, fundamental disciplines regarding materials science, chemistry, medicine and nanotechnology will be advanced.
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Affiliation(s)
- Xiaoqin Qian
- Department of Ultrasound, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212002, P. R. China
| | - Yuanyi Zheng
- Sixth Affiliated Hospital of Shanghai Jiaotong University & Shanghai Institute of Ultrasound in Medicine, Shanghai, 200233, P. R. China.
| | - Yu Chen
- State Key Laboratory of High Performance Ceramic and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
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Algarni AA, Alshuhri AH, Alonazi MM, Mourad MM, Bramhall SR. Focal liver lesions found incidentally. World J Hepatol 2016; 8:446-451. [PMID: 27028805 PMCID: PMC4807306 DOI: 10.4254/wjh.v8.i9.446] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Revised: 01/23/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision.
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Salvatore V, Gianstefani A, Negrini G, Allegretti G, Galassi M, Piscaglia F. Imaging Diagnosis of Hepatocellular Carcinoma: Recent Advances of Contrast-Enhanced Ultrasonography with SonoVue®. Liver Cancer 2016; 5:55-66. [PMID: 29234627 PMCID: PMC5704684 DOI: 10.1159/000367748] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Due to the ability to detect the typical contrast-imaging pattern for hepatocellular carcinoma (HCC), that is hyperenhancement in the arterial phase and hypoenhancement in the late phase on a cirrhotic background, contrast-enhanced ultrasonography (CEUS) was included in the American diagnostic algorithm for HCC in 2005. However, its role has been questioned because of the possibility of misdiagnosis of cholangiocarcinoma. The present review aims to describe the advantages and disadvantages of CEUS applications using Sonovue® for HCC. In particular there is focus on the accuracy of CEUS in detecting the typical HCC pattern, the CEUS patterns of intrahepatic cholangiocarcinoma (ICC), the risk of misdiagnosis with HCC, the diagnostic use of CEUS in cases of locoregional and systemic treatments, and the evaluation of response to antiangiogenic treatment using dedicated software.
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Affiliation(s)
| | | | | | | | | | - Fabio Piscaglia
- *Fabio Piscaglia, MD, PhD, Division of Internal Medicine, Department of Medical and Surgical Science, University of Bologna, S.Orsola-Malpighi Hospital, Via Albertoni 15, IT-40138, Bologna (Italy), Tel. +39 051 214 2568, E-Mail
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You MW, Kim SY, Kim KW, Lee SJ, Shin YM, Kim JH, Lee MG. Recent advances in the imaging of hepatocellular carcinoma. Clin Mol Hepatol 2015; 21:95-103. [PMID: 25834808 PMCID: PMC4379204 DOI: 10.3350/cmh.2015.21.1.95] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented.
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Affiliation(s)
- Myung-Won You
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Department of Radiology, Eulji Hospital, Eulji University School of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moon-Gyu Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. ; Asan Liver Cancer Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Liu GJ, Wang W, Lu MD, Xie XY, Xu HX, Xu ZF, Chen LD, Wang Z, Liang JY, Huang Y, Li W, Liu JY. Contrast-Enhanced Ultrasound for the Characterization of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Liver Cancer 2015; 4:241-52. [PMID: 26779444 PMCID: PMC4702012 DOI: 10.1159/000367738] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
PURPOSE AND METHODS The ability of contrast-enhanced ultrasound (CEUS) to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is still controversial. We reviewed the CEUS imaging of 819 patients (HCC=546, ICC=273) with an established pathological diagnosis. The enhancement patterns of lesions and the diagnostic performance of CEUS were analyzed. RESULTS Arterial hyperenhancement followed by washout was observed in 92.3% (504/546) of the HCC lesions and 85.7% (234/273) of the ICC lesions on CEUS (p<0.05). Additionally, the ICCs presented contrast washout much earlier than the HCCs, with an average time of 27.5 seconds after injecting the contrast agent compared with 70.1 seconds for the HCCs (p<0.05). Peripheral rim-like enhancement was observed in 68.5% (187/273) of the ICCs, which was significantly more common than that in the HCCs (2.0%, 11/546) (p<0.05). When using arterial hyperenhancement with a washout phase later than 43 seconds after injecting the contrast agent and with no peripheral rim-like enhancement as the diagnostic criteria for HCC ≤5 cm in diameter, the area under the curve was 0.808, with 64.1% sensitivity, 97.4% specificity and 73.6% accuracy. CONCLUSIONS Although ICC may show the typical enhancement pattern of HCC on CEUS, peripheral rim-like enhancement and quick contrast washout show high efficiency in the differentiation of HCC from ICC.
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Affiliation(s)
- Guang-Jian Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China,*Ming-De Lu, MD, DMSc, Department of Medical Ultrasonics, Institute of Diagnostic and, Interventional Ultrasound, and Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080 (China), Tel. +86 20 8776 5183, E-Mail
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hui-Xiong Xu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zuo-Feng Xu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Zhu Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jin-Yu Liang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yang Huang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Li
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jin-Ya Liu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, and, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Wang H, Wang P, Li L, Zhang K, Wang X, Liu Q. Microbubbles Enhance the Antitumor Effects of Sinoporphyrin Sodium Mediated Sonodynamic Therapy both In Vitro and In Vivo. Int J Biol Sci 2015; 11:1401-9. [PMID: 26681919 PMCID: PMC4671997 DOI: 10.7150/ijbs.12802] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 07/20/2015] [Indexed: 11/29/2022] Open
Abstract
Objectives: To evaluate the anti-cancer effect of sonodynamic therapy combined with microbubbles both in vitro and in vivo. Methods: Cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide and guava viacount assays. Annexin V-FITC/PI staining was adopted to analyze cell apoptosis rate. FD500 uptake assay was performed to assess cell membrane permeability changes. Tumor weight, mice weight and the visual image of tumor size were used to reflect the anti-tumor effect of this combined method. Histological change of tumor tissue after different treatments was measured through hematoxylin and eosin (H&E) staining. Results: Microbubbles can significantly enhance the cytotoxicity and necrocytosis rate induced by SDT treatment. Increased cell membrane permeability and more uptake of DVDMS were founded in SDT combined with microbubbles group. For in vivo experiments, SDT with microbubbles can significantly reduce tumor weight and size with pimping difference of mice weight compare with other treatment groups. In addition, microbubbles notably improved tumor tissue destruction caused by ultrasound and SDT treatment. Conclusion: The results suggest that microbubbles can markedly improve the anti-cancer effect of DVDMS mediate sonodynamic therapy both in vitro and in vivo.
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Affiliation(s)
- Haiping Wang
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
| | - Pan Wang
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
| | - Li Li
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
| | - Kun Zhang
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
| | - Xiaobing Wang
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
| | - Quanhong Liu
- Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, Shaanxi, China
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Shin SK, Kim YS, Choi SJ, Shim YS, Jung DH, Kwon OS, Choi DJ, Kim JH. Contrast-enhanced ultrasound for the differentiation of small atypical hepatocellular carcinomas from dysplastic nodules in cirrhosis. Dig Liver Dis 2015; 47:775-82. [PMID: 26043653 DOI: 10.1016/j.dld.2015.05.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 04/20/2015] [Accepted: 05/04/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Contrast-enhanced ultrasound is highly accurate in depicting the vascularity of liver nodules. The aim of this study was to evaluate the usefulness of contrast-enhanced ultrasound for the differentiation of hepatocellular carcinomas from dysplastic nodules in cirrhotic patients with small liver nodules showing atypical or not coincidental typical vascular pattern on two dynamic imaging techniques (computed tomography and magnetic resonance imaging). METHODS A total of 46 patients with cirrhosis and a liver nodule smaller than 3cm showing an atypical or non-coincident typical vascular pattern on two dynamic imaging techniques, who underwent liver contrast-enhanced ultrasound and ultrasound-guided liver biopsy, were retrospectively reviewed. Contrast-enhanced ultrasound findings were compared with histopathological and clinical data, and with the two dynamic imaging findings. RESULTS Significantly different contrast-enhanced ultrasound enhancement patterns were observed among dysplastic nodules, Edmondson grade I and grade II-III hepatocellular carcinomas. Ten out of 11 (90.9%) non-hypervascular hepatocellular carcinomas on two dynamic imaging techniques showed a hypervascular pattern on contrast-enhanced ultrasound, and these made it possible to distinguish hepatocellular carcinomas from dysplastic nodules. CONCLUSION Contrast-enhanced ultrasound is useful for the differentiation of hepatocellular carcinomas from dysplastic nodules in cirrhotic patients with small liver nodules.
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Affiliation(s)
- Seung Kak Shin
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Yun Soo Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
| | - Seung Joon Choi
- Department of Radiology, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Young Sup Shim
- Department of Radiology, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Dong Hae Jung
- Department of Pathology, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Oh Sang Kwon
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Duck Joo Choi
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Ju Hyun Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
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Abstract
Ultrasonography (US) is a safe and available real-time, high-resolution imaging method, which during the last decades has been increasingly integrated as a clinical tool in gastroenterology. New US applications have emerged with enforced data software and new technical solutions, including strain evaluation, three-dimensional imaging and use of ultrasound contrast agents. Specific gastroenterologic applications have been developed by combining US with other diagnostic or therapeutic methods, such as endoscopy, manometry, puncture needles, diathermy and stents. US provides detailed structural information about visceral organs without hazard to the patients and can play an important clinical role by reducing the need for invasive procedures. This paper presents different aspects of US in gastroenterology, with a special emphasis on the contribution from Nordic scientists in developing clinical applications.
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Affiliation(s)
- Svein Ødegaard
- Department of Medicine, National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital and Department of Clinical Medicine, University of Bergen , Bergen , Norway
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Feng Y, Qin XC, Luo Y, Li YZ, Zhou X. Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation. ULTRASOUND IN MEDICINE & BIOLOGY 2015; 41:1553-1560. [PMID: 25747937 DOI: 10.1016/j.ultrasmedbio.2015.01.026] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 01/18/2015] [Accepted: 01/26/2015] [Indexed: 06/04/2023]
Abstract
The aim of this retrospective study was to evaluate the efficacy of contrast-enhanced ultrasound (CEUS) washout rate in predicting hepatocellular carcinoma (HCC) differentiation. Two hundred seventy-one patients underwent liver resection for HCC between April 2008 and December 2012 after being examined by CEUS using the contrast agent SonoVue with a low mechanical index (<0.1) in a routine procedure. Contrast agent washout rates obtained from video images were divided into four categories from slow to fast: WR1 = no washout in all phases (slowest); WR2 = washout after 120 s from contrast injection (late-phase washout); WR3 = washout between 41 and 120 s from contrast injection (portal venous washout); WR4 = washout before 40 s from contrast injection (fastest washout rate). HCC nodules were graded as well, moderately and poorly differentiated. Spearman rank correlation and χ(2)-tests were used to assess group relationships and differences. Receiver operating characteristic curve analysis was used to determine the diagnostic predictive value of CEUS. Among the 271 patients, 18 (6.6%) had well differentiated, 150 (55.4%) had moderately differentiated and 103 (38.0%) had poorly differentiated HCC. Statistical tests indicated that washout rate was significantly correlated with tumor differentiation (p < 0.05), and the poorly differentiated HCCs had earlier washout. At the cutoff point of WR4, CEUS based on washout rate performed poorly in distinguishing poorly differentiated from moderately and well-differentiated HCCs, with a sensitivity, specificity and accuracy (area under the curve) of 24%, 97% and 0.68, respectively. However, at the cutoff point of WR2, the sensitivity, specificity and accuracy of CEUS in differentiating well-differentiated HCC from other HCCs were significantly better: 98%, 78% and 0.96, respectively. Thus, CEUS washout rate may have a role in identifying patients with well-differentiated HCC.
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Affiliation(s)
- Yan Feng
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Medical Imaging Pharmaceutical Lab, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xia-Chuan Qin
- Ultrasound Department, Nanchong Central Hospital, Nanchong, Sichuan Province, China
| | - Yan Luo
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yong-Zhong Li
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xiang Zhou
- Ultrasound Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Medical Imaging Pharmaceutical Lab, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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Cheng Q, Wang SS, Zhu XS, Li F. Evaluation of Tubal Patency with Transvaginal Three-dimensional Hysterosalpingo-contrast Sonography. ACTA ACUST UNITED AC 2015; 30:70-5. [DOI: 10.1016/s1001-9294(15)30014-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ren WP, Yu MH, Xu P. Value of contrast-enhanced ultrasound in assessing differentiation degree and pathological type of small hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2015; 23:907-913. [DOI: 10.11569/wcjd.v23.i6.907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the value of contrast-enhanced ultrasonography (CEUS) in assessing differentiation degree and pathological type of small hepatocellular carcinoma (SHCC).
METHODS: Ninety SHCC lesions examined by CEUS were retrospectively analyzed. The enhancement time and patterns were compared and analyzed according to the differentiation degree and pathological type of SHCC.
RESULTS: Of the 90 lesions, 48 had high differentiation, 30 had moderate differentiation, and 12 had low differentiation; 56 were trabecular type, 16 glandular type, 11 compact type and 7 cirrhotic type. Compared with patients with moderate or low differentiation lesions, those with high differentiation lesions showed significantly longer washout time (P = 0.000, P = 0.006). In the portal venous and late phases, the enhancement patterns showed statistically significant differences among lesions with different differentiation degrees (P = 0.000): compared with patients with moderate and high differentiation lesions, those with lower differentiation lesions showed a significantly higher rate of hypoechoic nodules and fast wash-in and wash-out enhancement pattern (P < 0.05). The difference of washout time was statistically significant among pathological types of SHCC (P = 0.021). Compared with the trabecular (100.12 s ± 33.00 s) and glandular types (98.98 s ± 30.20 s), the washout time was significantly shorter for the compact type (66.20 s ± 10.54 s). In the portal venous and late phases, the difference of enhancement patterns was statistically significant among pathological types of SHCC (P = 0.000, P = 0.000). In the trabecular, glandular and compact types, 77%, 75%, and 100% of lesions exhibited a fast wash-in and wash-out enhancement pattern, respectively. However, for the cirrhotic type, all lesions exhibited a fast wash-in and slow wash-out enhancement pattern.
CONCLUSION: CEUS may provide valuable information for assessing differentiation degree and histopathologic type of SHCC. More studies are needed to provide more evidence.
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Li W, Wang W, Liu GJ, Chen LD, Wang Z, Huang Y, Liu JY, Xie XY, Lu MD. Differentiation of Atypical Hepatocellular Carcinoma from Focal Nodular Hyperplasia: Diagnostic Performance of Contrast-enhanced US and Microflow Imaging. Radiology 2015; 275:870-9. [PMID: 25584708 DOI: 10.1148/radiol.14140911] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE To evaluate diagnostic performance of contrast-enhanced (CE) ultrasonography (US) and microflow (MF) imaging in differentiation of atypical hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH). MATERIALS AND METHODS Institutional review board approval was obtained, and informed consent was waived. A total of 103 patients (mean age, 43.9 years; age range, 17-75 years) were included; 38 patients with HCC and 65 with FNH underwent CE US, and vascular architecture pattern (VAP) and arrival time parametric (ATP) images were analyzed. Resident and staff radiologists independently and retrospectively reviewed CE US, VAP, and ATP images. χ(2) test and logistic regression analysis were applied to identify specific features of FNH or HCC on CE US and MF images. To compare diagnostic performance of CE US with or without MF imaging, four sets of criteria were assigned: (a) routine CE US alone, (b) VAP and CE US, (c) ATP imaging and CE US, and (d) all three methods in combination. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of resident and staff radiologists were analyzed. Cohen κ statistic was used to assess agreement of CE US and MF imaging features between staff and resident radiologists. RESULTS MF imaging offered significant improvements over most detection rates achieved with routine CE US signs in both groups. For staff radiologists, AUCs from criteria sets 3 (AUC = 0.873, P < .05) and 4 (AUC = 0.887, P < .05) were significantly higher than AUC from criteria set 1 (AUC = 0.835). For resident radiologists, specificity (71% and 69% vs 25%, P < .01) and accuracy (78% and 79% vs 50%, P < .01) of criteria sets 3 and 4 were significantly higher than those of criteria set 1. Moreover, AUCs for criteria sets 2 (AUC = 0.728, P < .05), 3 (AUC = 0.823, P < .01), and 4 (AUC = 0.857, P < .01) were significantly higher than those for criteria set 1 (AUC = 0.667). CONCLUSION When compared with routine CE US, MF imaging can more effectively depict specific features and offers improved diagnostic performance in the differentiation of atypical HCC from FNH, especially when used by resident radiologists. Online supplemental material is available for this article.
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Affiliation(s)
- Wei Li
- From the Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound (W.L., W.W., G.J.L., L.D.C., Z.W., Y.H., J.Y.L., X.Y.X., M.D.L.), and Department of Hepatobiliary Surgery (M.D.L.), The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080, China
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Chung YE, Kim KW. Contrast-enhanced ultrasonography: advance and current status in abdominal imaging. Ultrasonography 2014; 34:3-18. [PMID: 25342120 PMCID: PMC4282229 DOI: 10.14366/usg.14034] [Citation(s) in RCA: 116] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 09/10/2014] [Accepted: 09/12/2014] [Indexed: 12/12/2022] Open
Abstract
In the field of contrast-enhanced ultrasonography (US), contrast agents are classified as either first- or second-generation agents depending on the gas within the microbubbles. In the case of first-generation contrast agents, a high-mechanical-index technique is used and only intermittent scanning is possible due to the early destruction of the microbubbles during the scanning. The use of second-generation contrast agents in a low-mechanical-index technique enables continuous scanning. Besides the detection and characterization of focal liver lesions, contrastenhanced US is helpful in the monitoring of radiofrequency ablation therapy and in the targeting step of an US-guided biopsy. Recently, there has been a demand for new criteria to evaluate the treatment response obtained using anti-angiogenic agents because morphologic criteria alone may not reflect the treatment response of the tumor and contrast-enhanced US can provide quantitative markers of tissue perfusion. In spite of the concerns related to its cost-effectiveness, contrast-enhanced US has the potential to be more widely used as a complimentary tool or to substitute the current imaging modalities in some occasions.
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Affiliation(s)
- Yong Eun Chung
- Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
| | - Ki Whang Kim
- Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea
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de Sio I, Iadevaia MD, Vitale LM, Niosi M, Del Prete A, de Sio C, Romano L, Funaro A, Meucci R, Federico A, Loguercio C, Romano M. Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: A single-center retrospective study. United European Gastroenterol J 2014; 2:279-287. [PMID: 25083285 PMCID: PMC4114116 DOI: 10.1177/2050640614538964] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 05/12/2014] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the leading cause of death amongst cirrhotic patients. Its diagnosis and discrimination from non-HCC malignant lesions in cirrhosis includes contrast enhanced computed tomography (CECT), contrast enhanced magnetic resonance imaging (CEMRI), or, in selected cases, liver biopsy. The role of contrast-enhanced ultrasonography (CEUS) is still controversial. AIMS To evaluate whether, by selecting an appropriate 'time to wash-out' cut-off value, CEUS capability of discriminating between HCC and non-HCC malignancies in cirrhotic patients may be enhanced. METHODS We enrolled 282 cirrhotic patients who underwent CEUS at our institute, from January 2008 to January 2012, for focal liver lesions (FLLs) detected at ultrasound (US). We used liver biopsy and subsequent histological evaluation as the gold standard for correct classification of FLLs. We calculated the area under receiver operator characteristic curves for CEUS to distinguish patients with HCC from those with non-HCC malignancies. The best 'time to wash-out' cut-off values were selected. RESULTS HISTOLOGICAL DIAGNOSIS OF FLLS WAS AS FOLLOWS: 34 benign lesions (i.e. 25 regenerative nodules and 9 dysplastic nodules) and 248 malignant lesions (223 well-to-moderately differentiated HCCs; 7 poorly-differentiated HCCs; 5 intrahepatic colangiocellular carcinomas (ICCs); 5 primary non-Hodgkin B-cell lymphomas (NHBLs); and 8 metastatic liver tumors). A time to wash-out > 55 s identified patients with HCC with the highest level of accuracy (92.7%). Similarly, a time to wash-out ≤ 55 s correctly identified the vast majority of the non-HCC malignancies (100% sensitivity, 98.2% specificity and diagnostic accuracy of 98.3%). CONCLUSIONS CEUS is an accurate and safe procedure for discriminating FLLs in cirrhotic patients, especially when a cut-off time to wash-out of 55 s is chosen as a reference value.
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Affiliation(s)
| | - Maddalena D Iadevaia
- Department of Clinical and Experimental Medicine ‘Magrassi-Lanzara’, Second University of Naples, Naples, Italy
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D'Onofrio M, Crosara S, De Robertis R, Canestrini S, Cantisani V, Morana G, Mucelli RP. Malignant focal liver lesions at contrast-enhanced ultrasonography and magnetic resonance with hepatospecific contrast agent. ULTRASOUND : JOURNAL OF THE BRITISH MEDICAL ULTRASOUND SOCIETY 2013; 22:91-8. [PMID: 27433201 DOI: 10.1177/1742271x13513888] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to compare the diagnostic accuracy of the late phase of CEUS and the hepatobiliary phase of CE-MR with Gd-BOPTA in the characterization of focal liver lesions in terms of benignity and malignancy. A total of 147 solid focal liver lesions (38 focal nodular hyperplasias, 1 area of focal steatosis, 3 regenerative nodules, 8 adenomas, 11 cholangiocarcinomas, 36 hepatocellular carcinomas and 49 metastases) were retrospectively evaluated in a multicentre study, both with CEUS, using sulphur hexafluoride microbubbles (SonoVue, Bracco, Milan, Italy) and CE-MR, performed with Gd-BOPTA (Multihance, Bracco, Milan, Italy). All lesions thought to be malignant were cytohistologically proven, while all lesions thought to be benign were followed up. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and accuracy were calculated for the late phase of CEUS and the hepatobiliary phase of CE-MRI, respectively, and in combination. Analysis of data revealed 42 benign and 105 malignant focal liver lesions. We postulated that all hypoechoic/hypointense lesions on the two phases were malignant. The diagnostic errors were 13/147 (8.8%) by CEUS and 12/147 (8.2%) by CE-MR. Sensitivity, specificity, PPV, NPV and accuracy of the late phase of CEUS were 90%, 93%, 97%, 80% and 91%, 93%, 97%, 81% and 92% for the hepatobiliary phase of CE-MRI, respectively. If we considered both techniques, the misdiagnosis diminished to 3/147 (2%) and sensitivity, specificity, PPV, NPV and accuracy were 98%, 98%, 99%, 95% and 98%. The combination of the late phase of CEUS and the hepatobiliary phase of CE-MR in the characterization of solid focal liver lesions in terms of benignity and malignancy is more accurate than the two techniques used separately.
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Affiliation(s)
- M D'Onofrio
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - S Crosara
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - R De Robertis
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - S Canestrini
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
| | - V Cantisani
- Department of Radiology, University of Rome, Rome, Italy
| | - G Morana
- Department of Radiology, Treviso Hospital, Treviso, Italy
| | - R Pozzi Mucelli
- Department of Radiology, University Hospital G.B. Rossi, University of Verona, Verona, Italy
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Qu P, Yu X, Liang P, Cheng Z, Han Z, Liu F, Yu J. Contrast-enhanced ultrasound in the characterization of hepatocellular carcinomas treated by ablation: comparison with contrast-enhanced magnetic resonance imaging. ULTRASOUND IN MEDICINE & BIOLOGY 2013; 39:1571-1579. [PMID: 23830098 DOI: 10.1016/j.ultrasmedbio.2013.03.030] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 01/26/2013] [Accepted: 03/27/2013] [Indexed: 06/02/2023]
Abstract
The purpose of this study was to evaluate the clinical utility of low-mechanical-index contrast-enhanced ultrasound (CEUS) in assessing the response to percutaneous microwave ablation in patients with hepatocellular carcinoma by comparing the results with those of contrast-enhanced magnetic resonance imaging (CEMRI). Between August 2005 and July 2011, 182 patients with 231 lesions treated by microwave ablation were included in the study. One month after microwave ablation, CEUS and CEMRI were performed to evaluate therapeutic responses. The difference in diagnostic accuracy between the two methods was analyzed to evaluate the value of contrast-enhanced ultrasound after microwave ablation. The final diagnosis was based on computed tomography and MRI typical findings of therapeutic response of hepatocellular carcinoma, proven serum tumor marker levels and additional follow-up. The sensitivity of CEUS and CEMRI in evaluating the therapeutic effect of hepatocellular carcinoma was 86.5% and 84.6%; the specificity, 98.3% and 98.9%; and the accuracy, 95.7% and 95.7%.There was no significant statistical disparity between CEUS and CEMRI (p > 0.05).The sensitivity, specificity and accuracy were 98.1, 97.2 and 97.8% when CEUS was used in combination with CEMRI to evaluate the therapeutic response of hepatocellular carcinoma to microwave ablation. CEUS examination was proven to be a tolerable and easy modality for assessment of the therapeutic effect of microwave ablation and can provide results comparable to those obtained with CEMRI. Combining the results of these two examinations may reduce false-positive and false-negative diagnoses.
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Affiliation(s)
- Peng Qu
- Department of Intentional Ultrasound, Chinese Liberation Army General Hospital, Beijing, China
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Jang JY, Kim MY, Jeong SW, Kim TY, Kim SU, Lee SH, Suk KT, Park SY, Woo HY, Kim SG, Heo J, Baik SK, Kim HS, Tak WY. Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions. Clin Mol Hepatol 2013; 19:1-16. [PMID: 23593604 PMCID: PMC3622850 DOI: 10.3350/cmh.2013.19.1.1] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2012] [Revised: 03/08/2012] [Accepted: 03/14/2012] [Indexed: 12/12/2022] Open
Abstract
The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.
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Affiliation(s)
- Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
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Zheng SG, Xu HX, Lu MD, Xie XY, Xu ZF, Liu GJ, Liu LN. Role of contrast-enhanced ultrasound in follow-up assessment after ablation for hepatocellular carcinoma. World J Gastroenterol 2013; 19:855-865. [PMID: 23430451 PMCID: PMC3574882 DOI: 10.3748/wjg.v19.i6.855] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 12/03/2012] [Accepted: 12/25/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).
METHODS: A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT). The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d. Both images of follow-up CEUS and CECT were reviewed by radiologists. The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTP-free. LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule. The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci. On CEUS and CECT, LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e., hyper-enhancing during the arterial phase and washout in the late phase). With CECT as the reference standard, the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.
RESULTS: During a follow-up period of 1-31 mo (median, 4 mo), 169 paired CEUS and CECT examinations were carried out for the 141 patients. For a total of 221 ablated lesions, 266 comparisons between CEUS and CECT findings were performed. Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT, there was significant difference (P < 0.001). In comparison with CECT, the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13, respectively; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%, 97.4%, 81.8%, 94.4% and 92.3%, respectively. Meanwhile, 131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT, there was also significant difference (P < 0.05). In comparison with CECT, the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65, respectively; the sensitivity, specificity, PPV, NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%, 92.0%, 92.4%, 76.7% and 84.0%, respectively.
CONCLUSION: The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparison with CECT.
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Pei XQ, Liu LZ, Xiong YH, Zou RH, Chen MS, Li AH, Cai MY. Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma. Br J Radiol 2013; 86:20120536. [PMID: 23392189 DOI: 10.1259/bjr.20120536] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE To explore the potential of quantitative analysis of contrast-enhanced ultrasonography (CEUS) in differentiating focal nodular hyperplasia (FNH) from hepatocellular carcinoma (HCC). METHODS 34 cases of FNH and 66 cases of HCC (all lesions <5 cm) were studied using CEUS to evaluate enhancement patterns and using analytic software Sonoliver® (Image-Arena™ v.4.0, TomTec Imaging Systems, Munich, Germany) to obtain quantitative features of CEUS in the region of interest. The quantitative features of maximum of intensity (IMAX), rise slope (RS), rise time (RT) and time to peak (TTP) were compared between the two groups and applied to further characterise both FNH and HCC with hypoenhancing patterns in the late phase on CEUS. RESULTS The sensitivity and specificity of CEUS for diagnosis of FNH were 67.6% and 93.9%, respectively. For quantitative analysis, IMAX and RS in FNHs were significantly higher than those in HCCs (p<0.05), while RT and TTP in FNHs were significantly shorter (p<0.05). Both the 11 FNHs and 62 HCCs with hypo-enhancing patterns in the late phase were further characterised with their quantitative features, and the sensitivity and specificity of IMAX for diagnosis of FNH were 90.9% and 43.5%, RS 81.8% and 80.6%, RT 90.9% and 71.0%, and TTP 90.9% and 71.0%, respectively. CONCLUSION The quantitative features of CEUS in FNH and HCC were significantly different, and they could further differentiate FNH from HCC following conventional CEUS. ADVANCES IN KNOWLEDGE Our findings suggest that quantitative analysis of CEUS can improve the accuracy of differentiating FNH from HCC.
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Affiliation(s)
- X-Q Pei
- Department of Ultrasound, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Riccabona M. Application of a second-generation US contrast agent in infants and children--a European questionnaire-based survey. Pediatr Radiol 2012; 42:1471-80. [PMID: 23052725 DOI: 10.1007/s00247-012-2472-5] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2011] [Revised: 06/26/2012] [Accepted: 07/10/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND No US contrast agent (US-CA) is currently licensed for use in children. OBJECTIVE To survey the off-label use in children of a second-generation US-CA. MATERIALS AND METHODS Questionnaires were e-mailed to European paediatric radiologists, who were asked about their experience with the second-generation US-CA Sonovue® (Bracco, Milan, Italy). Number of examinations per indication and adverse effects were recorded. Examinations were categorised by intravenous or intracavitary use of US-CA. RESULTS Out of 146 respondents, 88 stated that they did not perform contrast-enhanced US in children, but 36 of these (44%) would appreciate paediatric approval. Forty-five centres reported 5,079 examinations in children (age mean: 2.9 years; range: birth-18 years, M/F: 1/ 2.8). The majority (4,131 [81%] in 29 centres) were intravesical applications. The minority (948 [19%] in 30 centres) were intravenous applications. No adverse effects had been recorded from intravesical use. Six minor adverse effects (skin reaction, unusual taste, hyperventilation) had been recorded after five intravenous studies (0.52%). CONCLUSION Responses suggest a favourable safety profile of this second-generation US-CA in children. It also demonstrates a demand for such US-CA from paediatric radiologists.
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Affiliation(s)
- Michael Riccabona
- Department of Radiology, Division of Paediatric Radiology, Universitätsklinikum LKH Graz, Auenbruggerplatz 34, 8036, Graz, Austria.
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Salvatore V, Bolondi L. Clinical impact of ultrasound-related techniques on the diagnosis of focal liver lesions. Liver Cancer 2012; 1:238-46. [PMID: 24159588 PMCID: PMC3760469 DOI: 10.1159/000343838] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Since its introduction in clinical practice, ultrasound technology has greatly impacted patient management, particularly in the case of liver diseases, where hepatologists usually perform ultrasound examinations. Clinicians are increasingly aware of the great potential of ultrasound waves and of the recent innovations that exploit the mechanical properties of ultrasound waves. Thus, at present, not only B-mode ultrasound but also contrast-enhanced ultrasound and, more recently, elastosonography are used worldwide in various settings. This review aims to describe why clinicians should be aware of ultrasound-based techniques, how they should use these techniques for assessing focal liver lesions, and how these techniques impact patient management. We will review the clinical potential of ultrasound-related techniques, starting from lesion detection, moving to characterization, and concluding with their utility in guiding treatments and analyzing their effects.
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Affiliation(s)
| | - Luigi Bolondi
- *Luigi Bolondi, MD, Division of Internal Medicine, Policlinico S.Orsola-Malpighi, Alma Mater Studiorum-University of Bologna, Via Albertoni 15, Bologna 40138 (Italy), Tel. +39 051636 2260, E-Mail
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